We have devised an in vitro experiment model and a system of ultra micro analysis that permits direct experimental measurement on many of the physicochemical parameters relevant to caries attack. The model consists of an enamel section cemented on one side to a glass plate, and on the other side to a 100 micron glass dish, in such a way as to leave the natural surface of the tooth exposed. Microscopic wells, 20 to 150 microns in diameter, are drilled through the dish and into sound and carious regions of the enamel. Enamel saturated solutions of various acids are then deposited in the wells, and water-saturated mineral oil, maintained at a fixed CO2 partial pressure, is poured into the dish to prevent evaporation. After equilibration of the section for a week with this same saturated solution, the solution in contact with the enamel surface is changed to an undersaturated solution of the same acids. The composition of the solution in the wells and the membrane potentials developed from the well to the outside solution are then followed as a function of time with ion selective micro electrodes and microcolorimetric techniques which we have devised. We have, through the use of these techniques, obtained experimental information about the mechanism of caries which (1) provides a set of boundary conditions that must be considered in all models of the process, and (2) points toward procedures by which the demineralization may be arrested or reversed. The goals of the research are: (1) to characterize the basic features of the decay process with a systematic inclusion in our experimental system of various factors relevant to the oral situation; (2) to use our model, in a simulation of the decay process which resembles the in vivo situation, so that both the driving force for demineralization and the response of the lesion will be monitored; and (3) to device new ultramicro techniques for dental research.